Triphenylphosphine → HCID 178441719, compound

To a solution of 6-butyl-3-(4-hydroxyphenyl)-2-methyl-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}pyrimidin-4(3H)-one (1.2 g), 4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanol (1.2 g) and triphenylphosphine (1.4 g) in tetrahydrofuran (12 mL) was added dropwise diisopropyl azodicarboxylate (1.9 M toluene solution, 2.8 mL). After stirring for 2 hr, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and a mixture of the residue, hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.3 g) and dimethyl sulfoxide (9 mL) was stirred overnight at 90° C. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (9 mL). N,N′-carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.28 mL) were added, and the mixture was stirred at room temperature for 30 min. Tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 2.5 mL) was added, and the mixture was stirred overnight at 50° C. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogen sulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound (0.45 g, 33%) as an amorphous solid.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. additiona mixture of the residue, hydroxylammonium chloride (0.87 g), sodium hydrogen carbonate (1.3 g) and dimethyl sulfoxide (9 mL)
6. stirringwas stirred overnight at 90° C
7. additionThe reaction mixture was diluted with ethyl acetate
8. washwashed with water
9. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
10. customThe solvent was evaporated under reduced pressure
11. dissolutionThe residue was dissolved in tetrahydrofuran (9 mL)
12. additionN,N′-carbonyldiimidazole (0.3 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.28 mL) were added
13. stirringthe mixture was stirred at room temperature for 30 min
14. additionTetrabutylammonium fluoride (1.0 M tetrahydrofuran solution, 2.5 mL) was added
15. stirringthe mixture was stirred overnight at 50° C
16. additionThe reaction mixture was diluted with ethyl acetate
17. washwashed with 5% aqueous potassium hydrogen sulfate solution
18. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
19. customThe solvent was evaporated under reduced pressure
20. customthe residue was purified by silica gel column chromatography

ORD record

ord-6571a35c261b4f4b83ff0dba05e0d177

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2